Interleukin-4 (IL-4) is a potent lymphokine that mediates a wide variety of functions on both hematopoietic and non-hematopoietic cells. Both in vivo and in vitro, it controls the production of IgE antibodies by regulating the process through which B cells switch to the expression of immunoglobulin of that isotype. Among T cells from naive donors, very few (about 1/1000) are capable of producing IL-4 in response to a polyconal stimulant such as immobilized anti-CD3 antibody. Immunization of mice in such a way as to induce high levels of IgE, such as infection with parasitic nematodes or injection of anti-IgD antibody, results in the appearance of large numbers of T cells that can produce IL-4. In vitro priming systems bave been developed through which T cells can develop into IL-4 producing cells. These systems depend upon the action of IL-4 itself on precursors of IL-4-producing cells. Such priming can be achieved both by polyclonal stimulants and, using mice transgenic for a T cell receptor specific for cytochrome c, by antigen-specific stimulation. IL-4 is also produced by FcepsilonRI+ cells in response to cross-linkage of FCepsilonRI, of FcgammaRIII or to treatment with ionomycin. In bone marrow cell cultures grown for 5-7 days with IL-3, the principal IL-4 producing cell is FcepsilonRI+, c-kit-. Upon isolation, such cells are strikingly enriched in basophils, strongly suggesting that this cell is the predominant hematopoietic cell, other than the T cell, that produces IL-4 in responses to a receptor-mediated stimulation. The capacity of such cells to produce IL-4 is markedly augmented by treatment with IL-3. Current evidence suggests that IL-3 functions by increasing the strength of the signal generated by cross-linkage of FcepsilonRI, as shown by increase in tyrosine phosphorylation of certain substrates in response to FcepsilonRI cross-linkage in mast cells that had been precultured in IL-3.